Acid-Catalyzed Decomposition of 1-Alkyltriazolines: A Mechanistic Study

Richard H. Smith, Brian D. Wladkowski, Jesse E. Taylor, Erin J. Thompson, Brunon Pruski, John R. Klose, A. W. Andrews, Christopher J. Michejda

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

1-Alkyltriazolines are five-membered cyclic triazenes containing the unusual Z-configuration for the triazene moiety. The hydrolytic decomposition of these compounds in aqueous or mixed acetonitrileaqueous buffers leads predominantly to the formation of the corresponding 1-alkylaziridines and lesser amounts of 2-(alkylamino)ethanols, alkylamines, and acetaldehyde. The latter two products presumably result from hydrolysis of a rearrangement product, N-ethylidenealkylamine. Neither the nature of the 1-alkyl group nor the pH of the medium greatly influences the product distribution, although decomposition in purely aqueous buffers slightly reduces the aziridine yields. The rate of hydrolysis of 1-alkyltriazolines is about twice as fast as that of the analogous acyclic 1,3,3-trialkyltriazenes and varies in the order tert-butyl > isopropyl > ethyl > butyl > methyl > propyl > benzyl. The mechanism of the decomposition is specific acid-catalyzed (A1) involving rapid reversible protonation followed by rate-limiting formation of a 2-(alkylamino)ethyldiazonium ion. The slopes of the log κobs versus pH plots are near −1.0. The solvent deuterium isotope effect, kH2O/kD2O, is in all cases <1.0 and ranges from 0.58 for 1-methyltriazoline to 0.86 for 1-benzyltriazoline. The rate of decomposition shows no significant dependence on the concentration of the buffer acid. The proposed mechanism involves rate-limiting formation of a 2-(alkylamino)ethyldiazonium ion, which is then partitioned among several competing product formation pathways. 1-Alkyltriazolines are potent direct-acting mutagens in the alkylation-sensitive TA 1535 strain of Salmonella typhimurium. A clear, dose-dependent mutagenicity is observed. At the highest dose level, various 1-alkyltriazolines have activities roughly equivalent to that of the potent methylating agent, 1,3-dimethyltriazene. At low levels of substrate, 1-alkyltriazolines are significantly more active than 1,3-dimethyltriazene, with mutagenicity following the order benzyl > methyl > ethyl.

Original languageEnglish (US)
Pages (from-to)2097-2103
Number of pages7
JournalJournal of Organic Chemistry
Volume58
Issue number8
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Acid-Catalyzed Decomposition of 1-Alkyltriazolines: A Mechanistic Study'. Together they form a unique fingerprint.

  • Cite this

    Smith, R. H., Wladkowski, B. D., Taylor, J. E., Thompson, E. J., Pruski, B., Klose, J. R., Andrews, A. W., & Michejda, C. J. (1993). Acid-Catalyzed Decomposition of 1-Alkyltriazolines: A Mechanistic Study. Journal of Organic Chemistry, 58(8), 2097-2103. https://doi.org/10.1021/jo00060a027